Methylsulfonylmethane Improves Knee Quality of Life in Participants with Mild Knee Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.

Methylsulfonylmethane (MSM) is a food ingredient present in small amounts in many foods, and its anti-inflammatory effects have been reported. We conducted a randomized, double-blind, placebo-controlled trial of oral consumption of MSM on mild pain of the knee joint in healthy Japanese participants. A total of 88 participants were enrolled in this study and randomly assigned to MSM consumption (n = 44) and placebo control (n = 44) groups. Both groups of participants took 10 tablets, each containing 200 mg MSM or lactose, per day for 12 weeks. The primary outcome of this study was measured values of the total score of the Japanese Knee Osteoarthritis Measure (JKOM) at 12 weeks after the test sample consumption. Safety evaluation was performed through physical examination, urine analysis, peripheral blood test, and medical interview. The total scores at 12 weeks in the MSM and placebo groups as the primary outcome were significantly different (p = 0.046). The health condition of JKOM also improved after MSM consumption (p = 0.032). The questionnaire results also suggested improvement in the knee and systemic health. This study indicated that MSM oral consumption improved both knee and systemic health conditions in healthy participants who experienced mild pain in the knee joint.

Inhibitory Effects of Parachlorella Beijerinckii Extracts on the Formation of Advanced Glycation End Products and Glycative Stress-Induced Inflammation in an In Vitro Skin Dermis-Like Model.

Advanced glycation end products (AGEs) are formed via a nonenzymatic glycosylation reaction called glycation. The formation and accumulation of AGEs increases in skin with age, contributing to the appearance of facial wrinkles and loss of skin elasticity. Therefore, inhibition of AGEs may delay skin aging. The microalgae Parachlorella beijerinckii has been used as a health food supplement for many years and contains carotenoids and vitamins that have antioxidant and anti-inflammatory effects. The aim of this study was to investigate whether Chlorella extract also has antiglycation activity. Antiglycation activity was measured using fluorescent AGEs, Nε-(carboxymethyl) lysine (CML), and Nε-(carboxymethyl) arginine (CMA) from glycated bovine serum albumin and type I collagen in vitro. A gel with a dermis-like structure consisting of collagen and a live fibroblast cell line was glycated with glyoxal. The content of fluorescent AGE, CML, and CMA, and the gel contraction activity were measured. In addition, to investigate the level of inflammation induced by the glycation of the collagen gel, the expression level of the receptor for AGEs and interleukin-8 were examined. Fat-solubleChlorella extract suppressed the formation of fluorescent AGEs, CML, and CMA in both models. These results indicated that Chlorella extract directly inhibited AGE formation. The collagen gel contracted over time during culturing, whereas contraction was inhibited in the glyoxal-treated collagen gel. Chlorella extract remarkably attenuated the glyoxal-induced gel contraction. Moreover, Chlorella extract substantially decreased the fluorescent AGEs, CML, and CMA in the collagen gels with glyoxal. Glyoxal exposure increased the expression levels of interleukin-8 and receptor for AGE proteins in collagen gels, while Chlorella extract inhibited this increase. This study showed that fat-solubleChlorella extract has a direct inhibitory effect on AGEs and decreases receptor expression for AGE-mediated inflammation by reducing AGEs. Chlorella may delay skin aging by inhibiting the formation and accumulation of AGEs.

Attenuating Effect of Chlorella Extract on NLRP3 Inflammasome Activation by Mitochondrial Reactive Oxygen Species.

The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to the pathogenesis of a wide variety of human diseases. Although many drugs and inhibitors have been developed to treat NLRP3-associated diseases, only limited clinical data support their efficacy and safety. Chlorella, a unicellular green alga that is widely and safely used as a food supplement, contains various antioxidants. In this study, we obtained a fat-soluble extract from Chlorella (CE) and demonstrated that it reduced NLRP3 inflammasome activation by inhibiting mitochondrial reactive oxygen species and caspase-1 activation. In addition, CE supplementation attenuated lipopolysaccharide-induced interleukin 1ß transcription through activation of hypoxia-inducible factor 1α in vitro and in vivo. As Chlorella is a safe and useful food supplement, it may be a practical pharmacological approach for treating NLRP3-driven diseases.

Safety evaluation of Chlorella sorokiniana strain CK-22 based on an in vitro cytotoxicity assay and a 13-week subchronic toxicity trial in rats.

The genus Chlorella contains unicellular green algae that have been used as food supplements. The purpose of this work was to evaluate the safety of the Chlorella sorokiniana strain CK-22 using powdered preparation (CK-22P) both by in vitro and in vivo assays. These included an experiment for cytotoxicity using Chinese hamster lung fibroblasts (V79 cells) and a 13-week repeated-dose oral toxicity trial using Wistar rats. The cytotoxicity was evaluated by MTT assay of a hot water extract (Hw-Ex) and 80% ethanol extract (Et-Ex) of CK-22P, and no effect on cell viability was observed. The 50% viability inhibitory effect (IC50) value for Hw-Ex and Et-Ex were estimated as greater than 73 and 17 µg/ml, respectively. In the subchronic toxicity test, pelleted rodent diet containing 0%, 2.5%, 5% or 10% CK-22P was given to Wistar rats (ten animals/sex/groups) for 13 weeks. During the experimental period, no CK-22P treatment-induced differences in general condition, body weight gain, food and water consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, histopathology, or animal death were observed. The no-observed-adverse-effect levels (NOAEL) were estimated to be 5.94 g/kg body-weight/day for males and 6.41 g/kg body-weight/day for females.

Demethylation of methylmercury and the enhanced production of formaldehyde in mouse liver.

Methylmercury (MeHg) is gradually changed to inorganic Hg after demethylation in animal tissues, and a selective quantification of inorganic Hg in the tissues is necessary to detect the reaction. We detected inorganic Hg formation in liver and kidney of mouse as early as 24 hr after MeHg injection. As an example of biological demethylation, the cytochrome P450 (P450)-mediated N-demethylation of drugs has been well documented, and formaldehyde was detected as a reaction product. Here we incubated mouse liver homogenate with added MeHg and observed a dose-dependent production of formaldehyde, as well as inorganic Hg formation. Since the amount of formaldehyde was approx. 500 times higher than that of the inorganic Hg that formed, the formaldehyde production would be stimulated by inorganic Hg formed from MeHg. We observed that inorganic Hg caused formaldehyde production, and it was enhanced by L-methionine and sarcosine. Thus, some biomolecules with S-methyl and N-methyl groups may function as methyl donors in the reaction. Using subcellular fractions of mouse liver, we observed that microsomal P450 did not participate in the demethylation of MeHg, but the greatest activity was located in the mitochondria-rich fraction. The addition of superoxide anion in the reaction mixture significantly enhanced the formaldehyde production, whereas Mn-superoxide dismutase depressed the reaction. Our present findings demonstrated that inorganic Hg formed by MeHg demethylation in mouse liver stimulated the endogenous formaldehyde production, and we observed that MeHg demethylation could be estimated by a formaldehyde analysis. Our results also suggested that superoxide anion is involved in the reaction.

Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study.

The anti-hypertensive effect of GABA-rich Chlorella was studied after oral administration for 12 weeks in the subjects with high-normal blood pressure and borderline hypertension in the placebo-controlled, double-blind manner in order to investigate if GABA-rich Chlorella, a dietary supplement, is useful in control of blood pressure. Eighty subjects with Systolic blood pressure (SBP) 130-159 mmHg or diastolic blood pressure (DBP) 85-99 mmHg (40 subjects/group) took the blinded substance of GABA-rich Chlorella (20 mg as gamma-aminobutyric acid) or placebo twice daily for 12 weeks, and had follow-up observation for an additional 4 weeks. Systolic blood pressure in the subjects given GABA-rich Chlorella significantly decreased compared with placebo (p < 0.01). Diastolic blood pressure had the tendency to decrease after intake of GABA-rich Chlorella. Neither adverse events nor abnormal laboratory findings were reported throughout the study period. Reduction of SBP in the subjects with borderline hypertension was higher than those in the subjects with high-normal blood pressure. These results suggest that GABA-rich Chlorella significantly decreased high-normal blood pressure and borderline hypertension, and is a beneficial dietary supplement for prevention of the development of hypertension.